{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:01:43Z","timestamp":1785225703716,"version":"3.55.0"},"reference-count":76,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["224326\/Z\/21\/Z"],"award-info":[{"award-number":["224326\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["300350\/Z\/23\/Z"],"award-info":[{"award-number":["300350\/Z\/23\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/T004991\/1"],"award-info":[{"award-number":["BB\/T004991\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/X000567\/1"],"award-info":[{"award-number":["BB\/X000567\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/Z514743\/1"],"award-info":[{"award-number":["BB\/Z514743\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020172","name":"Royal National Institute for Deaf People","doi-asserted-by":"publisher","award":["G94"],"award-info":[{"award-number":["G94"]}],"id":[{"id":"10.13039\/501100020172","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n Abstract<\/jats:title>\n \n Shaker\u20101<\/jats:italic>\n mice carry a spontaneous missense mutation in\n Myo7a<\/jats:italic>\n (\n \n Myo7a\n Sh1<\/jats:sup>\n <\/jats:italic>\n ) that interferes with the motor function of MYO7A. Mutation in the orthologous gene in humans causes syndromic (Usher 1B) or non\u2010syndromic forms of deafness. In hair cells, MYO7A is expressed throughout the stereocilia, where it has been implicated in tip\u2010link tensioning required for gating the mechanoelectrical transducer (MET) channel and setting its resting open probability (\n P<\/jats:italic>\n o<\/jats:sub>\n ). The\n \n Myo7a\n Sh1<\/jats:sup>\n <\/jats:italic>\n mutation progressively dysregulated the height of shorter stereocilia rows from the end of the first postnatal week onwards, associated with reduced MET current amplitude and hearing loss. Noise exposure exacerbated stereocilia dysfunction in\n \n Myo7a\n Sh1\/Sh1<\/jats:sup>\n <\/jats:italic>\n mice. Following the onset of maturation, hair cells from\n \n Myo7a\n Sh1\/Sh1<\/jats:sup>\n <\/jats:italic>\n mice showed normal resting\n P<\/jats:italic>\n o<\/jats:sub>\n and calcium sensitivity of the MET channel. In immature\n \n Myo7a\n Sh1\/Sh1<\/jats:sup>\n <\/jats:italic>\n hair cells, the resting\n P<\/jats:italic>\n o<\/jats:sub>\n was very small or absent in comparison to control cells, but it was restored by changing the membrane lipid bilayer fluidity or thickness by depleting cholesterol or PIP\n 2<\/jats:sub>\n . Bundle stiffness in immature IHCs was not affected by the absence of functional MYO7A but decreased after their onset of maturation in both genotypes. Expression of a subset of genes was affected similarly in immature\n \n Myo7a\n Sh1\/Sh1<\/jats:sup>\n <\/jats:italic>\n mice and in adult\n Myo7a<\/jats:italic>\n conditional knockout mice, indicating a common response pathway in\n Myo7a<\/jats:italic>\n \u2010deficient mice. This study reveals that MET channel gating might differ depending on hair cell developmental stage, and MYO7A is likely to influence, albeit indirectly, force transmission via the lipid bilayer to the MET channel and maintenance of the shorter rows of transducing stereocilia.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Shaker\u20101<\/jats:italic>\n mice carry a spontaneous missense mutation in the\n shaker\u20101<\/jats:italic>\n gene (\n \n Myo7a\n Sh1<\/jats:sup>\n <\/jats:italic>\n ) that interferes with the motor function of MYO7A, a protein expressed in hair\u2010cell stereocilia.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The absence of functional MYO7A (\n \n Myo7a\n Sh1\/Sh1<\/jats:sup>\n <\/jats:italic>\n mice) caused a progressive dysregulation in the height of the shortest two rows of stereocilia and the consequent loss of mechanoelectrical transduction (MET) current.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Although immature hair cells from\n \n Myo7a\n Sh1\/Sh1<\/jats:sup>\n <\/jats:italic>\n mice exhibited a markedly reduced resting open probability of their MET channels, this was restored upon maturation or following depletion of cholesterol or PIP\n 2<\/jats:sub>\n from the lipid bilayer.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Hair\u2010bundle stiffness was affected in immature inner hair cells from\n \n Myo7a\n Sh1\/Sh1<\/jats:sup>\n <\/jats:italic>\n mice, suggesting that MYO7A is not required for establishing the resting tension of the tip links gating the MET channels.\n <\/jats:p>\n <\/jats:list-item>\n \n We conclude that MYO7A is crucial for the structural integrity of the MET complex and transport of key proteins required to transfer forces efficiently from the lipid bilayer to the MET channel.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp289623","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:00:51Z","timestamp":1770962451000},"page":"2152-2175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myosin 7a is required for maintaining the transducing stereocilia and for force transmission to the MET channel during cochlear hair cell development"],"prefix":"10.1113","volume":"604","author":[{"given":"Anna","family":"Underhill","sequence":"first","affiliation":[{"name":"School of Biosciences University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Webb","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1303-6710","authenticated-orcid":false,"given":"Fiorella C.","family":"Grandi","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, Institute de Myologie, Centre de Recherche en Myologie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1054-3901","authenticated-orcid":false,"given":"Adam J.","family":"Carlton","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Yi","family":"Jeng","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield Sheffield UK"},{"name":"Neuroscience Institute University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1429-4145","authenticated-orcid":false,"given":"Corn\u00e9 J.","family":"Kros","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Sussex Falmer, Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8770-7628","authenticated-orcid":false,"given":"Walter","family":"Marcotti","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield Sheffield UK"},{"name":"Neuroscience Institute University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-007-9004-5"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi031"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2295"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201411173"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04589-8"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2318270121"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf689"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017114108"},{"key":"e_1_2_5_10_1","doi-asserted-by":"crossref","unstructured":"Caprara G. A. Kim Y. Jun S. Li S. Kim U. Shin J.\u2010B. &Peng A. W.(2025).PIP2\u2010Tmie interactions drive mammalian hair cell slow adaptation independently of myosin motors. Biorxiv.https:\/\/doi.org\/10.1101\/2025.04.01.646713","DOI":"10.1101\/2025.04.01.646713"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600494"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409920111"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06307-w"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.03.033"},{"issue":"9","key":"e_1_2_5_15_1","article-title":"Clarin\u20102 is essential for hearing by maintaining stereocilia integrity and function","volume":"11","author":"Dunbar L. A","year":"2019","journal-title":"European Molecular Biology Organization Molecular Medicine"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10833"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1351-17.2017"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0439-x"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3172"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(86)90222-4"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1997.0087"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/374062a0"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1028"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)00058-7"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20513"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104161108"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3071-12.2012"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.04.006"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100809-151502"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.6.1287"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.09.020"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-003-4021-2"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470942390.mo110059"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2221744120"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06091"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016486509127014"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.12.029"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/28401"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15936-z"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1690-14.2014"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0697-188"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1086\/280276"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00653.x"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-4624.1997.00020.x"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0693-06.2006"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0342-07.2007"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1964.00750040430011"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016486509124579"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1374901"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2022.102132"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18312"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200051109"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.09.018"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.07.033"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2023.108817"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2782-09.2009"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3011-15.2016"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200310055"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007097"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.4.557"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4251-05.2006"},{"key":"e_1_2_5_64_1","first-page":"65","article-title":"Age\u2010related changes in the C57BL\/6J mouse cochlea. I. Physiological findings","volume":"254","author":"Shnerson A.","year":"1982","journal-title":"Brain Research"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(83)90028-7"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02483"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02743"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.125021"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.08.110192.001353"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43473"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2414707122"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2016.10.002"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqz010"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/374060a0"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0697-191"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15864"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP289623","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP289623","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP289623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:39:11Z","timestamp":1785224351000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP289623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,12]]},"references-count":76,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1113\/JP289623"],"URL":"https:\/\/doi.org\/10.1113\/jp289623","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,12]]},"assertion":[{"value":"2025-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}